ABSTRACT Over 640,000 US adults suffer from ESRD, >95% of whom receive hemodialysis (HD) for the rest of their life or until transplantation. Kidney disease and HD significantly impact cognitive function, especially higher-order executive function. Only 13% of HD patients have normal cognition; HD patients experience executive function impairment at a rate 3-fold higher than the general population, leading to hospitalization, disability, and death. Studies of older adults suggest that the only effective interventions for preserving executive function are cognitive training (CT) and/or exercise training (ET). These modalities have not been tested for executive function preservation in HD patients; even younger HD patients suffer substantial executive function impairment and could benefit from these interventions. HD frequency (3 sessions a week) and duration (4-6 hours/session) makes HD patients a ?captive audience? for intradialytic CT and/or ET to mitigate executive function decline. In preliminary studies, HD patients reported spending most of their time watching TV; intradialytic CT and/or ET could replace these passive activities. In preliminary studies, 87% of nephrology providers believed that their patients would be interested in intradialytic CT and 83% believed that their patients would be interested in intradialytic ET. Among HD patients, 67% wanted to improve their cognition through CT and 71% wanted to improve their strength and cognition through ET while undergoing HD. To test the feasibility of intradialytic interventions, we conducted a pilot RCT of 20 HD patients, comparing standard of care to CT or ET; even in this pilot, we found that intradialytic CT and ET preserved executive function. As expected, executive function in patients receiving standard of care declined substantially by 3 months (difference=47.4 seconds, P=0.006); however, this decline was not seen among those receiving CT or ET. Compared with standard of care, the difference in mean change was -46.72 seconds (95% CI: -91.12, - 2.31; P=0.04) for CT and -56.21 seconds (95% CI: -105.86, -6.56; P=0.03) for ET. In just 3 months, CT and ET preserved executive function compared to a striking decline with standard of care. To properly test the impact of intradialytic CT and/or ET, on the executive function decline associated with HD, we propose the following aims: 1) To conduct an RCT to evaluate executive function decline in the setting of intradialytic CT and/or ET, 2) To quantify the effects of intradialytic CT and/or ET on ESRD-specific clinical outcomes, 3) To quantify the effects of intradialytic CT and/or ET, on patient-centered outcomes. Through this RCT, we will learn the impact of two potential non-pharmacological interventions, cognitive and exercise training, in preserving executive function during HD. If successful, this will improve HD outcomes of >640,000 adults with ESRD. For the first time, we will have validated, beneficial activities replace the typical passive activities of HD patients. Our findings will be implementable in dialysis centers across the country to help reduce the decline in executive function.